Safety and Immunogenicity of BBV121

A phase 1, multicenter, double-blind, placebo-controlled, randomised (intra group) clinical trial to evaluate the safety, tolerability and immunogenicity of two-doses of three-sequentially escalating cohort (2.5 µg, 5 µg and 10 µg) of BBV121 (inactivated adsorbed Zika Virus Vaccine) compared with Placebo (Alum) administered intramuscularly on Day 0 and 28 in healthy adult Dengue Sero-Negative (Group 1) and Dengue Sero-Positive (Group 2) male and female volunteers.

Participants will be assigned to sequential escalating dose level groups to receive vaccinations at 2.5 µg, 5 µg, or 10 µg or Placebo on Day 0 and 28 with follow-up for 12 months from initial administration of the investigational product.

Immunogenicity testing on Day 0, 28 and 56, and post-study at the end of Month 6, 9 and 12 after the initial administration of the investigational product.

Safety tests (laboratory and clinical investigations) will be done during Screening, Day 0, 28, 56, and post-study at Month 6, 9 and 12 months after the initial administration of the investigational product.

Inclusion criteria

• Normal healthy male and female volunteers aged between 18 and 65 years weighing at least 50kgs of body weight
• Ability to comprehend the full nature and purpose of the study, including possible risks and adverse events; ability to co-operate with the Investigator and to comply with the requirements of the entire study
• Signed written informed consent prior to inclusion in the study
• Seronegative for Zika by ELISA
• Dengue sero-negative at baseline by screening laboratory evaluation, confirmed by Dengue IgG by ELISA method for Group 1 participants
• Dengue seropositive at baseline by screening laboratory evaluation, confirmed by Dengue IgG by ELISA method for Group 2 participants
• Dengue vaccination or suffered from Dengue viral fever for Group 2 volunteers
• No history of yellow fever vaccination
• No history of vaccination to Japanese encephalitis vaccination
• Since active (live) ZIKV infection is known to cause teratogenicity, women of child-bearing potential should agree to use medically effective contraception (oral contraception, barrier methods, spermicide, etc.), preferably double contraception or have a partner who is sterile from enrollment to 3 months following the last injection, or have a male partner who is medically unable to induce pregnancy.
• Sexually active men who are considered sexually fertile must agree to use either a barrier method of contraception, preferably double contraception during the study, and agree to continue the use for at least 3 months following the last injection, or have a partner who is permanently sterile or is medically unable to become pregnant.
• A negative urine or serum pregnancy test before administration of investigational vaccine on day of screening (Serum Pregnancy Test), and Day 0 and Day 28 (both days Urine Pregnancy Test)
• No history of clinically significant immunosuppressive or autoimmune disease.
• Laboratory investigations must be within normal limits

• Hemoglobin >10gm/dL
• WBC (white blood cells) >4000/mm3
• Platelets >100,000/mm3
• Bilirubin and AST/ ALT <1.5 x ULN (upper limit of normal)
• Creatinine <1.5 x ULN for the clinical laboratory
• Not currently or within the previous 4 weeks taking immunosuppressive agents (excluding inhaled, topical skin and/or eye drop-containing corticosteroids, low-dose methotrexate, or corticosteroids at a dose less than 20 mg/day).
• Patients should be otherwise healthy as determined by physical examination, medical history, and no significant abnormality in any of the clinical parameters including ECG and Chest X-ray.
• Willing to allow storage and future use of biological samples for Zika virus related research.

Exclusion criteria

• Administration of an investigational vaccine or drug either currently or within 30 days of first BBV121 vaccination
• Previous receipt of an investigational vaccine or drug for the treatment or prevention of Zika virus
• Administration of any vaccine within 4 weeks of first dose
• Administration of any monoclonal or polyclonal antibody product within 4 weeks of the first dose of BBV121 vaccination
• Administration of any blood product within 3 months of first dose
• Pregnancy or breast feeding or plans to become pregnant during the study
• Positive serologic test for HIV, hepatitis B surface antigen (HBsAg); or any potentially communicable infectious disease as determined by the Principal Investigator or Medical Monitor
• Positive serologic test for hepatitis C (exception: successful treatment with confirmation of sustained virologic response);
• Chronic liver disease or cirrhosis
• Immunosuppressive illness including hematologic malignancy, history of solid organ or bone marrow transplantation
• Current or anticipated concomitant immunosuppressive therapy (excluding inhaled, topical skin and/or eye drop-containing corticosteroids, low-dose methotrexate, or corticosteroids at a dose less than 20 mg/day)
• Current or anticipated treatment with TNF-alpha inhibitors such as infliximab, adalimumab, and etanercept
• Prior major surgery or any radiation therapy within 4 weeks of enrolment
• Any pre-excitation syndromes, e.g., Wolff-Parkinson-White syndrome
• Presence of a cardiac pacemaker or automatic implantable cardioverter defibrillator
• Metal implants within 20 cm of the planned site(s) of injection
• Presence of keloid scar formation or hypertrophic scar at the planned site(s) of injection
• Prisoner or participants who are compulsorily detained (involuntary incarceration) for treatment of either a physical or psychiatric illness
• Active addictive drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements or assessment of immunologic endpoints
• Blood donations/ losses within 2 months of screening
• Significant orthostatic hypotension (i.e., a drop in systolic blood pressure of 30 mm Hg or more and/or a drop in diastolic blood pressure of 20 mmHg or more on standing)
• Prior radiotherapy in 30 days or less
• Significant pre-existing co-morbidities i. Cardiovascular

• Myocardial infarction within the last 6 months
• Congestive heart failure
• Unstable angina
• Active cardiomyopathy
• Cardiac arrhythmia
• Uncontrolled hypertension
• History of familial long QT syndrome or sudden cardiac death ii. Pulmonary disease requiring oxygen iii. Neurologic and psychiatric
• History of significant neurologic or psychiatric disorder that would preclude study compliance or ability to give informed consent iv. Rheumatic arthralgia
• Participants not having adequate hematologic reserve i. Hemoglobin <10gm/dL ii. WBC (white blood cells) <4000/mm3 iii. ANC (absolute neutrophils count) <2000/ mm3 iv. Platelets <100,000/mm3
• Inadequate hepatic function at screening as defined by:

i. Bilirubin >1.5 x ULN (upper limit of normal) ii. AST/ ALT >1.5 x ULN

• Inadequate renal function at screening as defined by:

i. Creatinine >1.5 x ULN for the clinical laboratory

• An unusual or abnormal diet, for whatever reason e.g. religious fasting
• Any illness or condition that in the opinion of the investigator may affect the safety of the participant or the evaluation of any study endpoint